The Central Role of Dendritic Cells in Immunity



Professional antigen-presenting cells play a major role in the initiation of immune responses against microbial and viral pathogens and are also critical for eliciting antitumor immunity. Dendritic cells are particularly potent antigen-presenting cells due to their ability to take up, process, and present antigen to both CD4+ and CD8+ T cells. They can promote inflammation at local sites of infection and act as carriers of antigen to lymphoid organs for T-cell priming. In this way, they bridge innate and adaptive immunity. The following section will review the many diverse subsets of both human and mouse dendritic cells and the phenotypic and functional changes they undergo following antigen exposure. Additionally, dendritic cell-directed T-cell differentiation will be discussed with some emphasis on dendritic cell plasticity and the role of dendritic cells in disease.


Dendritic Cell Experimental Autoimmune Encephalomyelitis Costimulatory Molecule Innate Immune Cell Dendritic Cell Maturation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Acosta-Rodriguez, E. V., Napolitani, G., Lanzavecchia, A. and Sallusto, F. 2007. Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells. Nat Immunol 8:942–949.PubMedCrossRefGoogle Scholar
  2. Al-Shami, A., Spolski, R., Kelly, J., Keane-Myers, A. and Leonard, W. J. 2005. A role for TSLP in the development of inflammation in an asthma model. J Exp Med 202:829–839.PubMedCrossRefGoogle Scholar
  3. Aliberti, J., Viola, J. P., Vieira-de-Abreu, A., Bozza, P. T., Sher, A. and Scharfstein, J. 2003. Cutting edge: bradykinin induces IL-12 production by dendritic cells: a danger signal that drives Th1 polarization. J Immunol 170:5349–5353.PubMedGoogle Scholar
  4. Amsen, D., Blander, J. M., Lee, G. R., Tanigaki, K., Honjo, T. and Flavell, R. A. 2004. Instruction of distinct CD4 T helper cell fates by different notch ligands on antigen-presenting cells. Cell 117:515–526.PubMedCrossRefGoogle Scholar
  5. Banchereau, J., Briere, F., Caux, C., Davoust, J., Lebecque, S., Liu, Y. J., Pulendran, B. and Palucka, K. 2000. Immunobiology of dendritic cells. Annu Rev Immunol 18:767–811.PubMedCrossRefGoogle Scholar
  6. Banchereau, J. and Steinman, R. M. 1998. Dendritic cells and the control of immunity. Nature 392:245–252.PubMedCrossRefGoogle Scholar
  7. Bianchi, M. E. 2007. DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol 81:1–5.PubMedCrossRefGoogle Scholar
  8. Cambi, A. and Figdor, C. G. 2003. Dual function of C-type lectin-like receptors in the immune system. Curr Opin Cell Biol 15:539–546.PubMedCrossRefGoogle Scholar
  9. Caux, C., Massacrier, C., Vanbervliet, B., Dubois, B., Van Kooten, C., Durand, I. and Banchereau, J. 1994. Activation of human dendritic cells through CD40 cross-linking. J Exp Med 180:1263–1272.PubMedCrossRefGoogle Scholar
  10. Conti, L., Casetti, R., Cardone, M., Varano, B., Martino, A., Belardelli, F., Poccia, F. and Gessani, S. 2005. Reciprocal activating interaction between dendritic cells and pamidronate-stimulated gammadelta T cells: role of CD86 and inflammatory cytokines. J Immunol 174:252–260.PubMedGoogle Scholar
  11. De Smedt, T., Van Mechelen, M., De Becker, G., Urbain, J., Leo, O. and Moser, M. 1997. Effect of interleukin-10 on dendritic cell maturation and function. Eur J Immunol 27:1229–1235.PubMedCrossRefGoogle Scholar
  12. Diebold, S. S. 2008. Determination of T-cell fate by dendritic cells. Immunol Cell Biol 86:389–397.Google Scholar
  13. Gilliet, M. and Liu, Y. J. 2002. Generation of human CD8 T regulatory cells by CD40 ligand-activated plasmacytoid dendritic cells. J Exp Med 195:695–704.PubMedCrossRefGoogle Scholar
  14. Groothuis, T. A. and Neefjes, J. 2005. The many roads to cross-presentation. J Exp Med 202:1313–1318.PubMedCrossRefGoogle Scholar
  15. Hermans, I. F., Silk, J. D., Gileadi, U., Salio, M., Mathew, B., Ritter, G., Schmidt, R., Harris, A. L., Old, L. and Cerundolo, V. 2003. NKT cells enhance CD4+ and CD8+ T cell responses to soluble antigen in vivo through direct interaction with dendritic cells. J Immunol 171:5140–5147.PubMedGoogle Scholar
  16. Idzko, M., la Sala, A., Ferrari, D., Panther, E., Herouy, Y., Dichmann, S., Mockenhaupt, M., Di Virgilio, F., Girolomoni, G. and Norgauer, J. 2002. Expression and function of histamine receptors in human monocyte-derived dendritic cells. J Allergy Clin Immunol 109:839–846.PubMedCrossRefGoogle Scholar
  17. Ito, T., Wang, Y.-H., Duramad, O., Hori, T., Delespesse, G. J., Watanabe, N., Qin, F. X.-F., Yao, Z., Cao, W. and Liu, Y.-J. 2005. TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand. J. Exp. Med. 202:1213–1223.PubMedCrossRefGoogle Scholar
  18. Kadowaki, N. 2007. Dendritic cells: a conductor of T cell differentiation. Allergol Int 56:193–199.PubMedCrossRefGoogle Scholar
  19. Kalinski, P., Vieira, P. L., Schuitemaker, J. H., de Jong, E. C. and Kapsenberg, M. L. 2001. Prostaglandin E(2) is a selective inducer of interleukin-12 p40 (IL-12p40) production and an inhibitor of bioactive IL-12p70 heterodimer. Blood 97:3466–3469.PubMedCrossRefGoogle Scholar
  20. Kawamura, K., Kadowaki, N., Kitawaki, T. and Uchiyama, T. 2006. Virus-stimulated plasmacytoid dendritic cells induce CD4+ cytotoxic regulatory T cells. Blood 107:1031–1038.PubMedCrossRefGoogle Scholar
  21. Ludwig, I. S., Geijtenbeek, T. B. and van Kooyk, Y. 2006. Two way communication between neutrophils and dendritic cells. Curr Opin Pharmacol 6:408–413.PubMedCrossRefGoogle Scholar
  22. Lutz, M. B. and Schuler, G. 2002. Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity? Trends Immunol 23:445–449.PubMedCrossRefGoogle Scholar
  23. Mahnke, K., Guo, M., Lee, S., Sepulveda, H., Swain, S. L., Nussenzweig, M. and Steinman, R. M. 2000. The dendritic cell receptor for endocytosis, DEC-205, can recycle and enhance antigen presentation via major histocompatibility complex class II-positive lysosomal compartments. J Cell Biol 151:673–684.PubMedCrossRefGoogle Scholar
  24. Matsushita, S. and Higashi, T. 2008. Human Th17 cell clones and natural immune responses. Allergol Int 57:135–140.PubMedCrossRefGoogle Scholar
  25. McWilliam, A. S., Napoli, S., Marsh, A. M., Pemper, F. L., Nelson, D. J., Pimm, C. L., Stumbles, P. A., Wells, T. N. C. and Holt, P. G. 1996. Dendritic cells are recruited into the airway epithelium during the inflammatory response to a broad spectrum of stimuli. J Exp Med 184:2429–2432.PubMedCrossRefGoogle Scholar
  26. Menges, M., Rossner, S., Voigtlander, C., Schindler, H., Kukutsch, N. A., Bogdan, C., Erb, K., Schuler, G. and Lutz, M. B. 2002. Repetitive injections of dendritic cells matured with tumor necrosis factor alpha induce antigen-specific protection of mice from autoimmunity. J Exp Med 195:15–21.PubMedCrossRefGoogle Scholar
  27. Moseman, E. A., Liang, X., Dawson, A. J., Panoskaltsis-Mortari, A., Krieg, A. M., Liu, Y. J., Blazar, B. R. and Chen, W. 2004. Human plasmacytoid dendritic cells activated by CpG oligodeoxynucleotides induce the generation of CD4+CD25+ regulatory T cells. J Immunol 173:4433–4442.PubMedGoogle Scholar
  28. Onfelt, B., Nedvetzki, S., Yanagi, K. and Davis, D. M. 2004. Cutting edge: Membrane nanotubes connect immune cells. J Immunol 173:1511–1513.PubMedGoogle Scholar
  29. Randolph, G. J., Angeli, V. and Swartz, M. A. 2005. Dendritic-cell trafficking to lymph nodes through lymphatic vessels. Nat Rev Immunol 5:617–628.PubMedCrossRefGoogle Scholar
  30. Reche, P. A., Soumelis, V., Gorman, D. M., Clifford, T., Liu, M., Travis, M., Zurawski, S. M., Johnston, J., Liu, Y. J., Spits, H., de Waal Malefyt, R., Kastelein, R. A. and Bazan, J. F. 2001. Human thymic stromal lymphopoietin preferentially stimulates myeloid cells. J Immunol 167:336–343.PubMedGoogle Scholar
  31. Reis e Sousa, C., Sher, A. and Kaye, P. 1999. The role of dendritic cells in the induction and regulation of immunity to microbial infection. Curr Opin Immunol 11:392–399.PubMedCrossRefGoogle Scholar
  32. Rimoldi, M., Chieppa, M., Salucci, V., Avogadri, F., Sonzogni, A., Sampietro, G. M., Nespoli, A., Viale, G., Allavena, P. and Rescigno, M. 2005. Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells. Nat Immunol 6:507–514.PubMedCrossRefGoogle Scholar
  33. Rustom, A., Saffrich, R., Markovic, I., Walther, P. and Gerdes, H. H. 2004. Nanotubular highways for intercellular organelle transport. Science 303:1007–1010.PubMedCrossRefGoogle Scholar
  34. Rutault, K., Alderman, C., Chain, B. M. and Katz, D. R. 1999. Reactive oxygen species activate human peripheral blood dendritic cells. Free Radic Biol Med 26:232–238.PubMedCrossRefGoogle Scholar
  35. Sabatte, J., Maggini, J., Nahmod, K., Amaral, M. M., Martinez, D., Salamone, G., Ceballos, A., Giordano, M., Vermeulen, M. and Geffner, J. 2007. Interplay of pathogens, cytokines and other stress signals in the regulation of dendritic cell function. Cytokine Growth Factor Rev 18:5–17.PubMedCrossRefGoogle Scholar
  36. Sallusto, F., Schaerli, P., Loetscher, P., Schaniel, C., Lenig, D., Mackay, C. R., Qin, S. and Lanzavecchia, A. 1998. Rapid and coordinated switch in chemokine receptor expression during dendritic cell maturation. Eur J Immunol 28:2760–2769.PubMedCrossRefGoogle Scholar
  37. Sato, K. and Fujita, S. 2007. Dendritic cells: nature and classification. Allergol Int 56:183–191.PubMedCrossRefGoogle Scholar
  38. Schnurr, M., Toy, T., Shin, A., Wagner, M., Cebon, J. and Maraskovsky, E. 2005. Extracellular nucleotide signaling by P2 receptors inhibits IL-12 and enhances IL-23 expression in human dendritic cells: a novel role for the cAMP pathway. Blood 105:1582–1589.PubMedCrossRefGoogle Scholar
  39. Schulz, O., Edwards, A. D., Schito, M., Aliberti, J., Manickasingham, S., Sher, A. and Reis e Sousa, C. 2000. CD40 triggering of heterodimeric IL-12 p70 production by dendritic cells in vivo requires a microbial priming signal. Immunity 13:453–462.PubMedCrossRefGoogle Scholar
  40. Soruri, A., Riggert, J., Schlott, T., Kiafard, Z., Dettmer, C. and Zwirner, J. 2003. Anaphylatoxin C5a induces monocyte recruitment and differentiation into dendritic cells by TNF-alpha and prostaglandin E2-dependent mechanisms. J Immunol 171:2631–2636.PubMedGoogle Scholar
  41. Soumelis, V., Reche, P. A., Kanzler, H., Yuan, W., Edward, G., Homey, B., Gilliet, M., Ho, S., Antonenko, S., Lauerma, A., Smith, K., Gorman, D., Zurawski, S., Abrams, J., Menon, S., McClanahan, T., de Waal-Malefyt Rd, R., Bazan, F., Kastelein, R. A. and Liu, Y. J. 2002. Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat Immunol 3:673–680.PubMedCrossRefGoogle Scholar
  42. Sozzani, S. 2005. Dendritic cell trafficking: More than just chemokines. Cytokine & Growth Factor Reviews 16:581–592.CrossRefGoogle Scholar
  43. Steinman, R. M. 1991. The dendritic cell system and its role in immunogenicity. Annu Rev Immunol 9:271–296.PubMedCrossRefGoogle Scholar
  44. Syme, R. M., Spurrell, J. C., Amankwah, E. K., Green, F. H. and Mody, C. H. 2002. Primary dendritic cells phagocytose Cryptococcus neoformans via mannose receptors and Fcgamma receptor II for presentation to T lymphocytes. Infect Immun 70:5972–5981.PubMedCrossRefGoogle Scholar
  45. Tailleux, L., Schwartz, O., Herrmann, J. L., Pivert, E., Jackson, M., Amara, A., Legres, L., Dreher, D., Nicod, L. P., Gluckman, J. C., Lagrange, P. H., Gicquel, B. and Neyrolles, O. 2003. DC-SIGN is the major Mycobacterium tuberculosis receptor on human dendritic cells. J Exp Med 197:121–127.PubMedCrossRefGoogle Scholar
  46. Tan, J. K. and O'Neill, H. C. 2005. Maturation requirements for dendritic cells in T cell stimulation leading to tolerance versus immunity. J Leukoc Biol 78:319–324.PubMedCrossRefGoogle Scholar
  47. van Beelen, A. J., Zelinkova, Z., Taanman-Kueter, E. W., Muller, F. J., Hommes, D. W., Zaat, S. A., Kapsenberg, M. L. and de Jong, E. C. 2007. Stimulation of the intracellular bacterial sensor NOD2 programs dendritic cells to promote interleukin-17 production in human memory T cells. Immunity 27:660–669.PubMedCrossRefGoogle Scholar
  48. van Vliet, S. J., den Dunnen, J., Gringhuis, S. I., Geijtenbeek, T. B. and van Kooyk, Y. 2007. Innate signaling and regulation of Dendritic cell immunity. Curr Opin Immunol 19:435–440.PubMedCrossRefGoogle Scholar
  49. Vermeulen, M. E., Gamberale, R., Trevani, A. S., Martinez, D., Ceballos, A., Sabatte, J., Giordano, M. and Geffner, J. R. 2004. The impact of extracellular acidosis on dendritic cell function. Crit Rev Immunol 24:363–384.Google Scholar
  50. Watkins, S. C. and Salter, R. D. 2005. Functional connectivity between immune cells mediated by tunneling nanotubules. Immunity 23:309–318.PubMedCrossRefGoogle Scholar
  51. Weaver, C. T., Hatton, R. D., Mangan, P. R. and Harrington, L. E. 2007. IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu Rev Immunol 25:821–852.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Immunology, University of Pittsburgh School of MedicineE1006 Biomedical Science TowerPittsburghUSA

Personalised recommendations